Creating the unforgettable: the short story of mapping long-term memory. Bicentennial Symposium

Memory is a binary process relying on a short-term form lasting minutes to forge and communicate with a long-term form lasting years. Yale's Bicentennial Symposium opened with a lecture elucidating the obscure process of long-term memory formation. From his decades of research, Nobel Laureate Eric Kandel offered insight into the molecular framework that is long term-memory.     

Recollections of Thomas John Wydrzynski

In appreciation of his contribution to the Photosystsem II research and commemoration of the book Photosystem II: The Light-Driven Water-Plastoquinone Oxido-Reductase, co-edited with Kimiyuki Satoh, I present here some of my recollections of Thomas John Wydrzynski and by several others with whom he has associated over the years at Urbana (Illinois), Berkeley (California), Standard Oil Company-Indiana (Illinois), Berlin (Germany), Gothenburg (Sweden), and Canberra (Australia). We not only recognize him for his unique career path in Photosystem II research, but also for his qualities as a collaborative scientist working on the only system on Earth that has the ability to oxidize water to molecular oxygen using the energy of sunlight.     

The Relationship between Event-Based Prospective Memory and Ongoing Task Performance in Chimpanzees (Pan troglodytes)

Prospective memory is remembering to do something at a future time. A growing body of research supports that prospective memory may exist in nonhuman animals, but the methods used to test nonhuman prospective memory differ from those used with humans. The current work tests prospective memory in chimpanzees using a method that closely approximates a typical human paradigm. In these experiments, the prospective memory cue was embedded within an ongoing task. Tokens representing food items could be used in one of two ways: in a matching task with pictures of items (the ongoing task) or to request a food item hidden in a different location at the beginning of the trial. Chimpanzees had to disengage from the ongoing task in order to use the appropriate token to obtain a higher preference food item. In Experiment 1, chimpanzees effectively matched tokens to pictures, when appropriate, and disengaged from the ongoing task when the token matched the hidden item. In Experiment 2, performance did not differ when the target item was either hidden or visible. This suggested no effect of cognitive load on either the prospective memory task or the ongoing task, but performance was near ceiling, which may have contributed to this outcome. In Experiment 3, we created a more challenging version of the task. More errors on the matching task occurred before the prospective memory had been carried out, and this difference seemed to be limited to the hidden condition. This finding parallels results from human studies and suggests that working memory load and prospective memory may have a similar relationship in nonhuman primates.     

Charles Darwin’s <Emphasis Type="BoldItalic">Beagle</Emphasis> Voyage,Fossil Vertebrate Succession,and “The Gradual Birth &; Death of Species”

The prevailing view among historians of science holds that Charles Darwin became a convinced transmutationist only in the early spring of 1837, after his Beagle collections had been examined by expert British naturalists. With respect to the fossil vertebrate evidence, some historians believe that Darwin was incapable of seeing or understanding the transmutationist implications of his specimens without the help of Richard Owen. There is ample evidence, however, that he clearly recognized the similarities between several of the fossil vertebrates he collected and some of the extant fauna of South America before he returned to Britain. These comparisons, recorded in his correspondence, his diary and his notebooks during the voyage, were instances of a phenomenon that he later called the “law of the succession of types.” Moreover, on the Beagle, he was following a geological research agenda outlined in the second volume of Charles Lyell’s Principles of Geology, which implies that paleontological data alone could provide an insight into the laws which govern the appearance of new species. Since Darwin claims in On the Origin of Species that fossil vertebrate succession was one of the key lines of evidence that led him to question the fixity of species, it seems certain that he was seriously contemplating transmutation during the Beagle voyage. If so, historians of science need to reconsider both the role of Britain’s expert naturalists and the importance of the fossil vertebrate evidence in the development of Darwin’s ideas on transmutation.     

The legacy of Hans Molisch (1856–1937), photosynthesis savant

Hans Molisch (1856–1937) was an exceptionally gifted and productive researcher who had broad interests in plant biology, physiology and biochemistry. In addition, he pioneered in isolating a number of species of purple photosynthetic bacteria in pure culture (including Rhodobacter capsulatus), which facilitated his discovery of basic aspects of bacterial photosynthesis. Molisch demonstrated conclusively that molecular oxygen is not produced by photosynthetic bacteria, and discovered the photoheterotrophic growth mode. The range of Molisch's research accomplishments was impressive, and he emerges as a major figure in the history of photosynthesis research. This essay reviews the numerous research contributions made by Molisch, particularly in regard to advancing knowledge of the several forms of photosynthetic metabolism. An English translation of his 1914 paper on the photosynthetic creation of visual images on leaves is included as an Appendix.     

质疑、创新与合理性——纪念《植物学通报》创刊主编曹宗巽先生诞辰100周年

为纪念《植物学通报》创刊主编曹宗巽先生诞辰100周年, 该文回顾了作者与曹先生结识的机缘和承接其未竟的黄瓜(Cucumis sativus)单性花发育调控机制研究衣钵的过程, 以及从实验结果到传统解释的逻辑困境, 通过追溯曹先生当年带回国内的有关植物性别研究早期专著而找到问题源头的柳暗花明的经历。同时分享了由于这段独特而宝贵的研究经历而引发的对什么是科学研究这个基本问题的思考, 希望对有志于探索未知自然的年轻人有所裨益。     

Scientific research at the Laboratoire Arago (Banyuls, France) in the twentieth Century: Edouard Chatton, the "master", and André Lwoff, the "pupil"

Edouard Chatton (1883–1947) began his scientific career in the Pasteur Institute, where he made several important discoveries regarding pathogenic protists (trypanosomids, Plasmodium, toxoplasms, Leishmania). In 1908 he married a "Banyulencque", Marie Herre; from 1920, he focused his research on marine protists. He finished his career as Professor at the Sorbonne (Paris) and director of the Laboratoire Arago in Banyuls-sur-mer, where he died in 1947. André Lwoff (1902–1994) lived several scientific lives in addition to his artistic and family life. But it is the study of protists that filled his first life after he encountered the exceptional Master who was Chatton. Lwoff's father was a psychiatrist and his mother an artist sculptor. He became a Doctor of Medicine in 1927 and then a Doctor of Sciences in 1932, his thesis dealing with biochemical aspects of protozoa nutrition. He met Chatton in 1921 and – until Chatton's death – their meetings, first in Roscoff and then in Banyuls-sur-mer, were numerous and their collaboration very close. Their monograph on apostome ciliates was one of the peaks of this collaboration. In 1938, Lwoff was made director of the Microbial Physiology Department at the Pasteur Institute in Paris, where he began a new life devoted to bacteria, and then to viruses, before pursuing his career as director of the Cancer Research Institute in Villejuif (France). Lwoff was awarded the Nobel Prize in Physiology or Medicine in 1965. He died in Banyuls in 1994. "Master" and "pupil" had in common perseverance in their scientific work, conception and observation, a critical sense and rigor but also a great artistic sensibility that painting and drawing in the exceptional surroundings of Banyuls-sur-mer had fulfilled. Electronic Publication     

A personal view from a long-lasting collaborator on the research strategies of Marshall Nirenberg

In this review, I summarized transition in Dr. Marshall Nirenberg’s research interests during 1970s, from a view of a long-lasting collaborator. Nirenberg switched his research filed to neurobiology after his success in deciphering genetic code and being honored with the Nobel Prize in Physiology or Medicine in 1968. His targets were to obtain genetically pure population of neurons, i.e. neuroblastoma clones, to make somatic hydrid cells, to culture neuronal and muscle cells, and to produce monoclonal antibodies against whole retinal or neuroblastoma cells. He studied neurotransmitters, receptors, cyclic nucleotides, cell differentiation, secretion, synapse formation, and chemical recognition. Especially he liked his hypothesis for opiate tolerance and dependency as a model of cellular memory. Through these studies, he seemed to devote all his time of about 50 years from 1960s to decoding brain memory processes.     

David Hubel and Torsten Wiesel

While attending medical school at McGill, David Hubel developed an interest in the nervous system during the summers he spent at the Montreal Neurological Institute. After heading to the United States in 1954 for a Neurology year at Johns Hopkins, he was drafted by the army and was assigned to the Neuropsychiatry Division at the Walter Reed Hospital, where he began his career in research and did his first recordings from the visual cortex of sleeping and awake cats. In 1958, he moved to the lab of Stephen Kuffler at Johns Hopkins, where he began a long and fruitful collaboration with Torsten Wiesel. Born in Sweden, Torsten Wiesel began his scientific career at the Karolinska Institute, where he received his medical degree in 1954. After spending a year in Carl Gustaf Bernhard's laboratory doing basic neurophysiological research, he moved to the United States to be a postdoctoral fellow with Stephen Kuffler. It was at Johns Hopkins where he met David Hubel in 1958, and they began working together on exploring the receptive field properties of neurons in the visual cortex. Their collaboration continued until the late seventies. Hubel and Wiesel's work provided fundamental insight into information processing in the visual system and laid the foundation for the field of visual neuroscience. They have had many achievements, including--but not limited to--the discovery of orientation selectivity in visual cortex neurons and the characterization of the columnar organization of visual cortex through their discovery of orientation columns and ocular-dominance columns. Their work earned them the Nobel Prize for Physiology or Medicine in 1981, which they shared with Roger Sperry.     

Atsushi Komamine (1929–2011): a tribute

Atsushi Komamine was one of the pioneers of plant tissue culture in Japan and a researcher with many friends throughout the world. His objective was to determine the potential capacities of plant cells, and he contributed considerably to plant tissue cultivation research by establishing several unique culture systems that controlled cell division and differentiation. He emphasized that the uniformity of cultured cells and the synchrony of the plant cell response at a high frequency were necessary to study the functions of plant cells using biochemical and molecular biological methods. He trained over 300 people, and many outstanding individuals in academia and industry emerged under his tutelage. He was an outstanding mentor: with his accommodating attitude, he was loved dearly by students and foreign researchers alike. He set up the Asia Pacific Association of Plant Tissue Culture and Agribiotechnology in 2000, and he established the international journal Plant Biotechnology Reports with Jang R. Liu in 2006, thereby contributing to Asian plant sciences. In addition to describing his achievements and activities, this article aims to paint a portrait of the man himself.     

The Relationship Between Voluntary and Involuntary Memory in Recognition and Recall

This article represents the continuation of a long and fruitful line of research begun more than forty years ago by A. A. Smirnov and his colleague P. I. Zinchenko. A major point made in this work is that remembering depends critically on the activities the subject engages in both at the time he is exposed to the materials and at the time memory is assessed.     

Contribution of late Professor T. C. Tung to the experimental embryology of Amphioxus

Professor T. C. Tung (Fig. 1) was a prominent experimental embryologist in China. He was born in Jin County, Zhejiang Province, China in 1902. After he obtained his Bachelor's degree from the Department of Biology, Fudan University, Shanghai in 1927, he was appointed as a teaching assistant in that department until he moved to Belgium in 1930. He studied as a graduate student in Professors A. Brachet and A. M. Dalcq's laboratory at the Universite Libre de Bruxelles, Belgium and obtained his Doctor of Science degree there in 1934. During that period, he made two short working visits to the Institute of Marine Biology in France and took one training course at Cambridge University (UK). In 1934, he was invited to return to China as a Full Professor to teach at several Chinese universities, (Shandong University in Qingdao, Shandong Province; the National University in Nanjing; and Fudan University in Shanghai). He spent 1 year at Yale University (USA) between 1948 and 1949 as an invited scientist in a joint research project and finally returned to China in 1949. He was Chairman of the Department of Zoology, Shandong University in Qingdao (1949-1952), Vice-President of Shandong University (1952-1960), Director of the Marine Biological Institute, the Chinese Academy of Sciences (CAS) in Qingdao (1949-1958), Director of the Institute of Oceanology (CAS) in Qingdao (1959-1966), Director of the Institute of Zoology (CAS) in Beijing (1960-1962), member of CAS since 1955, Vice-Chairman of the Biological and Geographical Division of CAS (1955-1958), Chairman of the Biological Division of CAS (1959-1979) and Vice-President of CAS in Beijing (1978-1979). In spite of his administrative duties, he spent most of his life conducting bench work in his laboratories at the Institutes of Oceanology and Zoology, CAS, respectively, until he passed away in March 1979. Professor Tung's main research interest was with classic experimental studies on the determination of the egg axis and symmetry planes of fertilized eggs, early differentiation and organizing substances of egg cytoplasm, induction between embryonic cells and cytoplasm in embryogenesis, immunological studies on nuclear transplanted eggs, and cell fusion etc., in several types of animals. He conducted his experiments on a number of invertebrates (ascidians and Amphioxus) and vertebrates (fish and amphibians) by means of very skillful microsurgical operations and the nuclear transplantation method. Among these topics, his studies on the organization and developmental potency of Amphioxus eggs were unique. His important contribution to this research field involved not only establishing a practical method for collecting and using this rare animal for experimental purposes, but also clarifying controversy about the nature and early development of its eggs. He also provided conclusive evidence to determine its evolutionary position between invertebrates and vertebrates. The present article briefly reviews the main results obtained by Professor Tung and his colleagues on Amphioxus. Although their original articles were written both in Chinese and English, many international readers may not even know those original works because they were only published in scientific journals inside China from the 1950s. Comments and discussion on the experimental results of Amphioxus research by Tung's group and those from other earlier authors are also included.     

The genius of Wilhelm Hofmeister: the origin of causal-analytical research in plant development

Friederich Wilhelm Benedikt Hofmeister (1824-1877) stands as one of the true giants in the history of biology and belongs in the same pantheon as Darwin and Mendel. Yet by comparison, he is virtually unknown. If he is known at all, it is for his early work on flowering plant embryology and his ground-breaking discovery of the alternation of generations in plants, which he published at age 27 in 1851. Remarkable as the latter study was, it was but a prelude to the more fundamental contributions he was to make in the study of plant growth and development expressed in his books on plant cell biology (Die Lehre von der Pfanzenzelle, 1867) and plant morphology (Allgemeine Morphologie der Gewächse, 1868). In this article we review his remarkable life and career, highlighting the fact that his scientific accomplishments were based largely on self-education in all areas of biology, physics, and chemistry. We describe his research accomplishments, including his early embryological studies and their influence on Mendel's genetic studies as well as his elucidation of the alternation of generations, and we review in detail his cell biology and morphology books. It is in the latter two works that Hofmeister the experimentalist and biophysicist is most manifest. Not only did Hofmeister explore the mechanisms of cytoplasmic streaming, plant morphogenesis, and the effects of gravity and light on their development, but in each instance he developed a biophysical model to integrate and interpret his wealth of observational and experimental data. Because of the lack of attention to the cell and morphology books, Hofmeister's true genius has not been recognized. After studying several evaluations of Hofmeister by contemporary and later workers, we conclude that his reputation became eclipsed because he was so far ahead of his contemporaries that no one could understand or appreciate his work. In addition, his basically organismic framework was out of step with the more reductionistic cytogenetic work that later came in vogue. We suggest that the translation of the cell and morphology books in English would help re-establish him as one of the most notable scientists in the history of plant biology.     

On the legacy of W.S. McCulloch

In this paper, we review McCulloch's legacy, from his early work in neurophysiology, and its relationship to his philosophical quest for an 'experimental epistemology' to his role in the cybernetics movement during the 1940s and 1950s and his contributions to the development of computer science and communication theory. There are three parts in chronological sequence. First, the period up to his work at Yale University with Dusser de Barenne, where he concentrated on the experimental study of the functional organization of sensory cortex. Second, the time of his Psychiatric Chair at the University of Chicago and the organization of the Macy Foundation Conferences. To this period corresponds the genesis and publication of the most influential and quoted work by McCulloch and Pitts: A Logical Calculus of the Ideas Immanent in Neurons Activity. Third, the period of his research activity at the Massachussetts Institute of Technology where he, Lettvin, Maturana and Pitts produced epochmaking papers on epistemological neurophysiology, the modelling of the reticular formation and other work with da Fonseca and Moreno-Díaz. We finally refer to the International Conference that took place in McCulloch's memory at the 25th anniversary of his death. Our main conclusion is that McCulloch's writings are still a source of inspiration from neurophysiology to artificial intelligence and robotics.     

Howard A. Schneiderman--Planetary Patriot

SYNOPSIS. This symposium on arthropod development is dedicatedto the memory of Howard A. Schneiderman, who died on December5, 1990. Howard devoted much of his professional life to researchon arthropods and was the author of numerous publications onthe developmental biology of moths and flies. At Case-WesternReserve University and at the University of California-Irvinehe founded research institutes devoted to developmental biologyon arthropods as well as other organisms. Howard Schneidermanchampioned the use of insect growth regulators, which derivedfrom his research on the chemistry and physiology of juvenilehormone, as environmentally innocuous methods of controllinginsect pests of our food and fiber. In recent years he was aproponent of the use of molecular biology to alter the plantgenome so that insect-resistant crops might be grown and therebyreduce the use of insecticides. His global perspective was evidentin his understanding of how biotechnology could be applied toworld agriculture. Moreover, he quickly achieved prominencein promoting industry-university relations in his capacity asSenior Vice President for Research and Development at the MonsantoCompany. The cooperation among academic and industrial institutionsthat he fostered stands as a model for such relationships. HowardSchneiderman's influence on science and its applications, andon the universityindustry interface was profound and will befelt for many years to come.     

The construction of a scientific model: Otto Warburg and the building block strategy

In the years 1919 to 1923, Otto Warburg published four papers that were to revolutionise the field of photosynthesis. In these articles, he introduced a number of new techniques to measure the rate of photosynthesis, put forward a new model of the mechanism and added a completely new perspective to the topic by attempting to establish the process’s efficiency in terms of the light quantum requirement. In this paper I trace the roots of Warburg’s series of contributions to photosynthesis research by exploring three different contexts of inspiration: Warburg’s own research into cell respiration, his father’s work on the quantum yield of photochemical reactions in general and the photosynthesis work carried out by Richard Willstätter and Arthur Stoll. When these influences are considered together, it becomes clear that Warburg implemented a Building Block Strategy in his research: rather than inventing his photosynthesis model from scratch, he availed himself of fragments from other contexts, which he then recombined in a new and innovative way. This way of working is considered to be standard practice in scientific research.     

Structural Components of Synaptic Plasticity and Memory Consolidation

Consolidation of implicit memory in the invertebrate Aplysia and explicit memory in the mammalian hippocampus are associated with remodeling and growth of preexisting synapses and the formation of new synapses. Here, we compare and contrast structural components of the synaptic plasticity that underlies these two distinct forms of memory. In both cases, the structural changes involve time-dependent processes. Thus, some modifications are transient and may contribute to early formative stages of long-term memory, whereas others are more stable, longer lasting, and likely to confer persistence to memory storage. In addition, we explore the possibility that trans-synaptic signaling mechanisms governing de novo synapse formation during development can be reused in the adult for the purposes of structural synaptic plasticity and memory storage. Finally, we discuss how these mechanisms set in motion structural rearrangements that prepare a synapse to strengthen the same memory and, perhaps, to allow it to take part in other memories as a basis for understanding how their anatomical representation results in the enhanced expression and storage of memories in the brain.Santiago Ramón y Cajal (1894) used the insights provided by his remarkable light microscopic observations of neurons selectively stained with the Golgi method to propose the first cellular theory of memory storage as an anatomical change in the functional connections between nerve cells, later called synapses (Sherrington 1897). For most of the last century, chemical synapses were thought to convey information in only one direction—from the presynaptic to the postsynaptic neuron. It now is clear that synaptic transmission is a bidirectional and self-modifiable form of cell–cell communication (Peters et al. 1976; Jessell and Kandel 1993). This appreciation of reciprocal signaling between pre- and postsynaptic elements is consistent with other forms of intercellular communication and provides a conceptual framework for understanding memory-induced changes in the structure of the synapse. Indeed, an increasing body of evidence suggests that trans-synaptic signaling and coordinated recruitment of pre- and postsynaptic mechanisms underlie consolidation of both implicit and explicit forms of memory storage (Marrone 2005; Hawkins et al. 2006; Bailey et al. 2008).Studies in a variety of systems have found that molecular mechanisms of consolidation and long-term storage of memory begin at the level of the synapse. Existing proteins are modified, signals are sent back to the nucleus so that specific genes are expressed, and gene products are transported back to the synapse where the local synthesis of new protein is triggered to allow for the remodeling, addition, and elimination of synapses (Bailey and Kandel 1985; Bailey et al. 1996; Kandel 2001; Bourne and Harris 2008, 2012). These structural components of synaptic plasticity are thought to represent a cellular change that contributes to both implicit and explicit memory consolidation (Greenough and Bailey 1988; Bailey and Kandel 1993; Bailey et al. 2005; Bourne and Harris 2008, 2012). The association between alterations in the structure and/or number of synapses and memory storage has led to numerous studies regarding the signaling pathways that might couple molecular changes to structural changes. In addition, parallel homeostatic mechanisms have been identified that can trigger synaptic scaling, which serves to stabilize the strengthened synapses while weakening or eliminating other synapses, thus providing specificity during memory consolidation (Bourne and Harris 2011; Schacher and Hu 2014).In this review, we compare and contrast structural changes at the synapse during both implicit and explicit memory consolidation, as well as the molecular signaling pathways that initiate the learning-induced structural changes versus those that serve to maintain these changes over time. Toward that end, we will focus on two experimental model systems and several prototypic forms of synaptic plasticity that we have worked on and that have been extensively studied as representative examples of memory storage: long-term habituation and sensitization of the gill-withdrawal reflex in Aplysia. These are examples of implicit memory consolidation and hippocampal-based long-term potentiation (LTP) and long-term depression (LTD), as candidate mechanisms for the synaptic plasticity underlying explicit memory storage in mammals. These will serve as useful points of comparison to consider similarities, differences, and still-existing limitations in our understanding of the functional significance of the structural synaptic plasticity recruited during the consolidation of both implicit and explicit forms of memory.     

From cognitive to neural models of working memory

Working memory refers to the temporary retention of information that was just experienced or just retrieved from long-term memory but no longer exists in the external environment. These internal representations are short-lived, but can be stored for longer periods of time through active maintenance or rehearsal strategies, and can be subjected to various operations that manipulate the information in such a way that makes it useful for goal-directed behaviour. Empirical studies of working memory using neuroscientific techniques, such as neuronal recordings in monkeys or functional neuroimaging in humans, have advanced our knowledge of the underlying neural mechanisms of working memory. This rich dataset can be reconciled with behavioural findings derived from investigating the cognitive mechanisms underlying working memory. In this paper, I review the progress that has been made towards this effort by illustrating how investigations of the neural mechanisms underlying working memory can be influenced by cognitive models and, in turn, how cognitive models can be shaped and modified by neuroscientific data. One conclusion that arises from this research is that working memory can be viewed as neither a unitary nor a dedicated system. A network of brain regions, including the prefrontal cortex (PFC), is critical for the active maintenance of internal representations that are necessary for goal-directed behaviour. Thus, working memory is not localized to a single brain region but probably is an emergent property of the functional interactions between the PFC and the rest of the brain.     

The bacteriophage, its role in immunology: how Macfarlane Burnet's phage research shaped his scientific style

The Australian scientist Frank Macfarlane Burnet-winner of the Nobel Prize in 1960 for his contributions to the understanding of immunological tolerance-is perhaps best recognized as one of the formulators of the clonal selection theory of antibody production, widely regarded as the 'central dogma' of modern immunology. His work in studies in animal virology, particularly the influenza virus, and rickettsial diseases is also well known. Somewhat less known and publicized is Burnet's research on bacteriophages, which he conducted in the first decade of his research career, immediately after completing medical school. For his part, Burnet made valuable contributions to the understanding of the nature of bacteriophages, a matter of considerable debate at the time he began his work. Reciprocally, it was while working on the phages that Burnet developed the scientific styles, the habits of mind and laboratory techniques and practices that characterized him for the rest of his career. Using evidence from Burnet's published work, as well as personal papers from the period he worked on the phages, this paper demonstrates the direct impact that his experiments with phages had on the development of his characteristic scientific style and approaches, which manifested themselves in his later career and theories, and especially in his thinking regarding various immunological problems.